The long-range objectives of the proposed work are to contribute to an understanding of the pathogenesis and immunology of cholera which will lead to rational and effective means of prophylaxis and treatment. As cholera is the prototype of an emerging group of enterotoxic enteropathies, the results should be applicable to other, more common, secretory diarrheal diseases. Our major specific immediate goals are: (a) to develop additional avirulent mutants of Vibrio cholerae which can harmlessly colonize the human intestine and which will elicit local immune responses which will be protective against cholera and immunologically related enterotoxic enteropathies, and (b) to develop a further understanding of the mechanism(s) by which V. cholerae attaches to intestinal epitheium, which may be pertinent to the pathogenesis and immunology of cholera.